AZD0754 for Prostate Cancer

(APOLLO Trial)

Recruiting at 13 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, up to 2 years

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called AZD0754 for people with metastatic prostate cancer. Researchers aim to evaluate how well this treatment works against tumors and its safety for patients. Participants should have prostate cancer that has spread and have experienced disease progression despite other treatments. Those who have tried certain cancer medications and still face challenges might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must continue any medical castration therapy if you are on it, and you cannot receive certain full-dose anticoagulants or recent anticancer therapies close to the study start. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that AZD0754 is likely to be safe for humans?

Research has shown that AZD0754 is effective against cancer cells in lab tests. However, specific safety information for AZD0754 in humans is not yet available. It remains in the early testing stages, where scientists primarily assess its safety for people. During these tests, they closely monitor any side effects and how well patients tolerate the treatment.

Although detailed safety data for AZD0754 is lacking, a similar drug, AZD3514, has been tested, providing researchers with some optimism about AZD0754's safety. Since this trial is in its early phases, safety continues to be a focus of study. Participants are carefully monitored to ensure they tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for metastatic prostate cancer, such as androgen deprivation therapy or chemotherapy, AZD0754 introduces a novel approach by targeting specific molecular pathways involved in disease progression. This treatment is unique because it acts on pathways that are less exploited by current therapies, potentially offering a new mechanism of action that could be more effective in slowing or stopping cancer spread. Researchers are excited about AZD0754 because it represents a shift towards more targeted therapy, which could lead to fewer side effects and better outcomes for patients.

What evidence suggests that AZD0754 might be an effective treatment for prostate cancer?

Research has shown that AZD0754, which participants in this trial will receive, may help treat advanced prostate cancer. In animal studies, AZD0754 successfully targeted and shrank tumors without causing harm. Early tests demonstrated its ability to kill cancer cells and increase the production of IFNγ, a protein that helps the immune system fight cancer. Although human trials are ongoing, these early findings suggest that AZD0754 could effectively treat this type of cancer. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic prostate cancer. Participants should meet specific health criteria to be eligible, but the exact inclusion and exclusion details are not provided.

Inclusion Criteria

My prostate cancer is growing despite hormone therapy.

My prostate cancer has spread, and it's not small cell or neuroendocrine type.

I have had treatments like abiraterone or taxane for prostate cancer, or I cannot or will not take taxane.

Exclusion Criteria

Participants with prior solid organ transplantation

I had cancer before, but it was treated over 2 years ago and is not likely to come back.

I have brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD0754 CAR T-cell therapy to evaluate safety, tolerability, and antitumour activity

Variable, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AZD0754

Trial Overview The study is testing AZD0754 CAR T-cell therapy's safety, how well people can handle it, and its effectiveness in treating metastatic prostate cancer.

How Is the Trial Designed?

Group I: AZD2287 Experimental Treatment 1 Intervention

AZD2287 is a novel imaging agent for STEAP2

Group II: AZD0754 Experimental Treatment 1 Intervention

AZD0754 monotherapy for treatment of participants with metastatic prostate cancer.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

ZIC5 is upregulated in prostate cancer, especially in metastatic cases, and its inhibition reduces cancer cell invasion and metastasis, indicating its role in promoting aggressive cancer behavior.

The study reveals that ZIC5 and the androgen receptor (AR) enhance each other's expression, contributing to metastasis and resistance to enzalutamide treatment, suggesting that targeting both ZIC5 and AR could be a promising strategy for treating advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AR-regulated ZIC5 contributes to the aggressiveness of prostate cancer. Tan, YF., Zhang, Y., Ge, SY., et al.[2022]

AZD3514 is an orally bioavailable drug that effectively inhibits both androgen-dependent and -independent signaling of the androgen receptor (AR), which is crucial for treating castration-resistant prostate cancer (CRPC).

The drug works through two mechanisms: it prevents the nuclear translocation of the AR and reduces the overall levels of the receptor, demonstrating significant antitumor activity in animal models, including juvenile male rats and the HID28 mouse model of CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Loddick, SA., Ross, SJ., Thomason, AG., et al.[2021]

In a study of 105 prostate cancer patients with bone metastases, combining zoledronic acid (ZA) with docetaxel-based chemotherapy improved bone progression-free survival (9.0 months vs. 6.0 months) and overall survival (19.0 months vs. 15.0 months) compared to chemotherapy alone.

While the combination treatment did not show a significant difference in prostate-specific antigen (PSA) response rates, it was found to be safe, with no notable differences in adverse events between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel with or without zoledronic acid for castration-resistant prostate cancer. Pan, Y., Jin, H., Chen, W., et al.[2021]

The study developed and validated an immunohistochemistry (IHC) method to assess androgen receptor (AR) levels in circulating tumor cells (CTCs) for patients undergoing treatment with AZD3514, a drug targeting prostate cancer.

Initial reproducibility tests showed almost perfect agreement between operators in scoring AR positivity (κ=0.94), but a bias in staining intensity was corrected through additional training, improving agreement to κ=0.81, demonstrating the method's reliability and potential for broader application in IHC techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells. Cummings, J., Sloane, R., Morris, K., et al.[2021]

In a study of 441 prostate tissue samples, MRP4 expression was found to be widely present in both benign and cancerous tissues, but it decreased as tumors progressed towards castrate-resistant disease.

Lower levels of MRP4 were linked to shorter PSA relapse-free survival times in androgen-dependent prostate cancer, suggesting that MRP4 expression could serve as a prognostic marker for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression. Montani, M., Hermanns, T., Müntener, M., et al.[2021]

In a study involving 60 hormone-naïve prostate cancer patients, the combination of combined androgen blockade (CAB) with zoledronic acid (ZA) significantly reduced the incidence of skeletal-related events (SREs) and bone pain compared to CAB alone.

Patients with a Gleason score of 8 or higher showed improved progression-free survival (PFS) when treated with CAB-ZA, suggesting that this combination therapy is particularly beneficial for those with more aggressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of combined androgen blockade with zoledronic acid treatment in prostate cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade trial on prostate cancer) study. Ueno, S., Mizokami, A., Fukagai, T., et al.[2022]

In a study of 302 men who underwent radical prostatectomy for localized prostate cancer, low expression of the biomarker zinc-alpha 2-glycoprotein (AZGP1) was linked to a significantly higher risk of biochemical failure, castration-based treatment, and developing castration-resistant prostate cancer over a median follow-up of 14 years.

The analysis showed that men with low AZGP1 expression had more than double the risk of aggressive outcomes compared to those with high expression, indicating that AZGP1 could be a valuable predictor for treatment decisions in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis. Kristensen, G., Berg, KD., Toft, BG., et al.[2020]

In a 7-year study involving patients with early, non-metastatic prostate cancer, adding bicalutamide (150 mg) to standard care significantly improved progression-free survival (PFS) for those with locally advanced disease, reducing the risk of progression by 34%.

However, in cases of localized disease, bicalutamide did not show a significant benefit in PFS, and there was no difference in overall survival between the treatment and standard care groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. Wirth, M., Tyrrell, C., Delaere, K., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06267729

Study of AZD0754 in Participants With Metastatic Prostate ... The purpose of this study is to evaluate the safety, tolerability, and antitumour activity of AZD0754 CAR T-cell therapy in participants with metastatic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10645390/

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2 ... These data reveal that human-murine cross-reactive STEAP2 CAR-Ts can effectively elicit antitumor activity without toxicity in in vivo models ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/24-254

A Phase 1-2 Study of AZD0754 CAR T-Cell Therapy in ... Researchers want to find the best dose of AZD0754 for people with prostate cancer. The patients in this study have prostate cancer that has metastasized (spread) ...

4. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A369

325 Armored STEAP2 CAR-T (AZD0754) alone and in ... Moreover, AZD0754 CAR-T treatment induced significant anti-tumor efficacy and corresponding IFNγ production in a panel of prostate PDX models ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393880/

Developmental Therapeutics in Metastatic Prostate Cancer An estimated 299,010 new cases of prostate cancer and an estimated 35,250 deaths will occur in the United States in 2024. The estimated number ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37966111/

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2 ... AZD0754 demonstrated potent and specific cytotoxicity against antigen-expressing cells in vitro despite TGF-β-rich conditions.

7. jci.org jci.org/articles/view/169655

Antitumor activity of AZD0754, a dnTGFβRII-armored ... AZD0754 demonstrated potent and specific cytotoxicity against antigen-expressing cells in vitro despite TGF-β–rich conditions.

8. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-i-ii-open-label-study-evaluate-safety-cellular-kinetics-and-efficacy-azd0754-achimeric-antigen-receptor-car-t-cell-therapy-directed-against-steap2-adult-participantswith-metastatic-prostate

A Phase I/II Open Label Study to Evaluate the Safety, Cellular ... The purpose of this study whether AZD0754 is safe to administer to people with prostate cancer that has spread to other parts of your body (metastatic) and ...

9. withpower.com withpower.com/trial/phase-2-prostatic-neoplasms-1-2024-bf8dd

AZD0754 for Prostate Cancer (APOLLO Trial) What safety data exists for AZD0754 in humans? There is no specific safety data available for AZD0754, but a similar compound, AZD3514, has been evaluated ...